Adoptive immunotherapy with donor lymphocyte infusions (DLI) is an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation. To identify the effector and target cell populations responsible for the elimination of the leukemic cells in vivo we developed an assay to measure the frequency of T lymphocyte precursor cells capable of suppressing leukemic progenitor cells. Target cells in this assay were CML cells that were cultured in the presence of stem cell factor, interleukin 3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and erythropoietin.[ 3 H]thymidine incorporation at day 7 represented the proliferation of the progeny of the CD34 ؉ CML progenitor cells, and not of the more mature CD34 ؊ CML cells. Effector cells were mononuclear cells, which were used in a limiting dilution analysis to measure the frequencies of CML progenitor cellinhibitory lymphocyte precursors (PCILp) in peripheral blood of seven patients before and after DLI for relapsed CML. In the six patients who entered complete remission, a 5-to 100-fold increase of PCILp was found during the clinical response. In the patient with resistant relapse the frequency of PCILp was <10 per ml before and after DLI. Leukemiareactive helper T lymphocyte precursor frequencies remained unchanged after DLI. A significant increase in cytotoxic T lymphocyte precursor frequency against more mature leukemic cells was found in only two responding patients. These results indicate that T cells specifically directed against CD34 ؉ CML progenitor cells mediate the antileukemic effect of DLI.Allogeneic stem cell transplantation (SCT) is potentially curative in patients with chronic myeloid leukemia (CML) not only by the cytoreductive effects of irradiation and chemotherapy, but also by a graft-versus-leukemia effect (1). Clinical evidence for this effect by the immunocompetent cells in the stem cell graft is supported by a lower risk of relapse in patients with graft-versus-host disease (GvHD) after transplantation (2), and an increased risk of relapse in patients treated with a syngeneic transplant (3) or a T cell-depleted transplant (4-6). Moreover, the transfusion of lymphocytes from the original stem cell donor in patients with a cytogenetic or hematological relapse of CML after SCT results in a complete remission in 70-80% of the patients (7-12). The response rate is lower in patients with relapsed CML in accelerated phase or blast crisis (10, 12). DLI is accompanied by GvHD and bone marrow aplasia in 90% and 35-50% of the patients, respectively (10, 12).The frequency of allo-reactive T cells in an HLA-identical donor that may react with patient leukocytes or leukemic cells is low (13-15). The development of acute GvHD and bone marrow aplasia during the responsive phase after DLI was associated with increased patient-reactive helper T lymphocyte precursor (HTLp) frequencies, as determined in a limiting dilution assay using cocultures of peripheral blood MNC after DLI...

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The curative effect of allogeneic stem cell transplantation (SCT) is due to a cytoreductive effect of chemotherapy and total body irradiation, and an additional immunological effect, which is attributed to T lymphocytes from the healthy stem cell donor.1 Clinical evidence for this graft-versusleukemia (GVL) effect is found in an increased incidence of relapse of the original disease after SCT with a T celldepleted stem cell graft.2-5 Moreover, a relapse of chronic myeloid leukemia (CML) after SCT can be successfully treated by the infusion of peripheral blood mononuclear cells (MNC) from the original stem cell donor.6-10 These

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